Self-Adherent Implants and Methods of Preparation

ABSTRACT

Implants are described herein which contain an activated adhesive on at least a portion of the surface of the implant. A release sheet may be positioned over at least a portion of the adhesive. Packages which contain the implants and methods of preparing the implants are also described.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a divisional application of U.S. patentapplication Ser. No. 13/549,915, filed Jul. 16, 2012, which is adivisional application of U.S. patent application Ser. No. 12/182,189,filed Jul. 30, 2008, now abandoned, which claims the benefit of andpriority to U.S. Provisional Application No. 60/999,079 filed on Oct.16, 2007, the disclosures of each of the above-identified applicationsare hereby incorporated by reference in their entirety.

BACKGROUND

1. Technical Field

The present disclosure relates to self-adherent medical implants andpackaging for such implants. Methods of preparing self-adherent implantsare also disclosed.

2. Background of Related Art

Currently methods for securing medical implants, e.g., surgical meshes,to tissue include the use of a variety of fasteners (such as tacks orstaples) alone or in combination with adhesives.

To work properly fasteners may need to be driven into specific areas ofthe implant as well as specific areas of the target tissue. As a result,the application of fasteners typically requires the use of graspers orother equipment to manipulate the implants and ensure that the fasteneris properly positioned relative to both the implant and the targettissue. Such manipulations, while necessary with conventional fasteners,may undesirably increase the duration of the surgical procedure. Inaddition, the fasteners support the implants only at the point ofpenetration and do not distribute the load across the entire surface ofthe implant.

Known methods of using adhesives to secure medical implants to targettissue normally require the implants to be contacted with the adhesiveimmediately prior to implantation, during the surgery. As a result, thesurgeon normally handles implants coated with adhesive materials. Theseadhesive materials may interact with any surface with which the implantcomes into contact, e.g., medical instruments, a surgeon's hands orgloves, tissue other than the intended target tissue, etc.

It would be advantageous to provide implants that do not require the useof a fastening device, and that reduce the likelihood that theadhesive-bearing implant will prematurely adhere to unintended surfacesthe implant may encounter prior to implantation.

SUMMARY

Accordingly, the implants described herein contain an adhesive on atleast a portion of the surface of the implant and a release sheetoverlying at least a portion of the adhesive.

Packages for containing implants having an activated adhesive positionedon at least a portion of a surface of the implant are also described.The package includes an internal surface overlying at least a portion ofthe activated adhesive when the package is closed, wherein at least aportion of the internal surface is a release sheet.

In embodiments, the package includes a first cavity containing anadhesive, a second cavity positioned adjacent the first cavity andconfigured to contain an implant and a rupturable barrier positionedbetween the first and second cavity. Rupture of the rupturable barrierallows the adhesive to communicate with at least a portion of the secondcavity or implant. Dispensers for activating such packaged implants arealso contemplated by this disclosure. The dispensers include acompartment containing the above-described packaged implant. Thecompartment includes a dispensing opening for allowing the passage ofthe packaged implant therethrough and a structure for rupturing therupturable barrier of the packaged implant

Methods for preparing a self-adherent implant are also described. Themethods include the steps of applying an activated adhesive on at leasta portion of the implant and overlying at least a portion of theactivated adhesive with a release sheet.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a side view of a packaged implant in accordance with anillustrative embodiment described herein.

FIG. 2 shows a side view of a packaged implant in accordance withanother illustrative embodiment described herein.

FIG. 3A shows a side view of a packaged implant in accordance with atwo-compartment illustrative embodiment described herein.

FIG. 3B shows a top view of the packaged implant of FIG. 3A.

FIG. 4 shows a cross-sectional view of an illustrative embodiment of adispenser for the packaged implant of FIG. 3A.

FIG. 5 shows an illustrative embodiment of an apparatus suitable forperforming a method of manufacturing an implant in accordance with thepresent disclosure.

FIGS. 6A-6C show an embodiment of a dispenser for the implants describedherein.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Medical implants that are self-adherent, packaging used to contain theimplants, dispensers for activating the packaged implants and methods ofpreparing the self-adherent implants are all described herein. Theimplants contain an adhesive on at least a portion of the surface of theimplant and a release sheet positioned over at least a portion of theadhesive.

As used herein, the term “implant” is used in the broadest sense andincludes any biocompatible material that can be inserted into a body(human or any other animal) and which may remain in that body for atleast some time. Some specific non-limiting examples of suitableimplants include surgical meshes, patches, suture anchors, slings,grafts, bone plates, drug delivery devices, wound dressings, wovendevices, non-woven devices, braided devices, adhesion barriers, tissuescaffolds, felts, pads, foams, films, fleeces, pledgets, buttresses, andother supportive medical devices. In some embodiments, the self-adherentimplant is used to support tissue in pelvic floor prolapse, any type ofhernia repair, cosmetic surgeries, arteriole bypass surgeries and woundclosures. In embodiments, the implant is a surgical mesh.

The implants described herein can be formed from any sterilizablematerial that has suitable physical properties for the intended use ofthe implant. For example, the implants can be made from bioabsorbable,non-bioabsorbable, natural or synthetic polymeric materials, metallicmaterials and combinations thereof. Some specific non-limiting examplesof suitable absorbable materials which may be utilized to form theimplants include trimethylene carbonate, caprolactone, dioxanone,glycolic acid, lactic acid, glycolide, lactide, alkyl derivatives oftrimethylene carbonate, delta.-valerolactone, β-butyrolactone,γ-butyrolactone, ε-decalactone, hydroxybutyrate, hydroxyvalerate,1,4-dioxepan-2-one (including its dimer1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one,6,6-dimethyl-1,4-dioxan-2-one and polymer blends, homopolymers,copolymers and combinations thereof. Some specific non-limiting examplesof suitable non-absorbable materials which may be utilized to form themedical implant include polyethylene, polypropylene, polyester,polyethylene terephthalate, polytetrafluoroethylene,polyaryletherketone, acrylic, polyamides, aramids, fluoropolymers,polybutester, silicone and flurocarbons cotton, linen, silk, polyamides,polyhexamethylene adipamide, polyhexamethylene sebacamide,polycapramide, polydodecanamide, and polyhexamethylene isophthalamide,polymer blends, homopolymers, copolymers and combinations thereof. Inaddition, the polymeric materials can include a naturally occurringbiological molecule, or a variant thereof, such as collagen, gelatin,cellulose, starches, polysaccharides, alginate, chitosan, hyaluronicacid and combinations thereof. Also, some examples of metallic materialsinclude, stainless steel, metal alloys, and shape-memory materials,e.g., nitinol.

The implants may contain any adhesive capable of adhering or attachingthe implant to the target tissue. The adhesive may be biodegradable,non-biodegradable, bioabsorbable, non-bioabsorbable, natural, synthetic,and any combination thereof. The adhesives may include, for example,α-cyanoacrylates, isocyanates, polyurethanes, polyamines, polyamides,polymethacrylates, polyacrylates, and other synthetic monomers andpolymers and combinations thereof. Some non-limiting examples of naturalmaterials that may be positioned on at least a portion of the implantinclude fibrin, collagen, albumin, thrombin, gelatin, proteins andcombinations thereof.

The adhesives may be activated at the time of application to theimplant, or may require activation subsequent to application to theimplant. By the term activated, it is meant that the adhesive is tackywithout any further treatment and will adhere to surfaces with which itcomes into contact. In embodiments, the adhesive is a material which isprepared to react with the target tissue to attach the implant withoutrequiring activation or the addition of an initiator, diluent orcross-linker. That is not to say that initiators, diluents andcross-linkers may not be used, but rather that in the interest ofefficiency, packaged implants which contain an activated adhesive areadvantageous.

The adhesive can be positioned on any portion of the implant and in anymanner suitable to coating an implant. In some embodiments, the adhesiveis positioned on an outer surface of the implant. In some embodiments,the adhesive is allowed to penetrate into the implant. Some suitablemethods for applying the adhesive to the medical device include, but arenot limited to, dipping, brushing, spraying, painting, dotting,layering, patterning and wiping. In some embodiments, the adhesive maybe applied by dip coating the medical implant directly into an adhesivesolution. In other embodiments, the adhesive is in the form of a solid,e.g., powder, particulate matter or coating layer which may be sprayed,wiped or brushed onto the surface of the implants.

In embodiments in which the implant may be used to support tissue,certain portions of the implant may require more adhesive to fullysupport a given tissue. It is envisioned that the adhesive may be placedonto the medical implant in any pattern, and in varying concentrations,to further enhance the implant's ability to adhere to and support thetarget tissue.

A release sheet is positioned over at least a portion of the adhesive.The release sheet is designed to prevent contact or interaction with theadhesive prior to implantation thereby allowing medical personnel tohandle the implant without fear of prematurely attaching the implant toan unintended surface. The release sheet also allows the implant to befolded, rolled or twisted in any manner while preventing the adhesivefrom contacting any portion of the implant thereby preventing theimplant from sticking to itself. The release sheet may be made from anybioabsorbable or non-bioabsorbable material which is non-reactive to theadhesive. Some examples include, but are not limited to, polylactones,polytetrafluoroethylene, polyolefins, metalized polymer films, metallicfoils and combinations thereof. In particularly useful embodiments, therelease sheet may be made from polytetrafluoroethylene.

In some embodiments, the release sheet is made of a material whichdissolves when placed in contact with water, saline or other naturalbodily fluids including blood, mucous, sweat, saliva and the like. Someexamples of dissolvable materials include, but are not limited to,polyvinyl pyrrolidones, polyethylene glycols, polyvinyl alcohols,polyacrylic acids, carboxymethylcellulose, alginates, hyaluronic acids,dextrans, polysaccharides, gelatins, and combinations thereof. Thedissolvable release sheet is designed to prevent contact or interactionwith the adhesive prior to implantation and expose the adhesive afterinteraction with a particular bodily fluid in which the release sheet isdissolvable.

Turning now to FIG. 1, implant 10 is shown containing an adhesive 12positioned on at least a portion of the surface 11 of implant 10 and arelease sheet 15 overlying at least a portion of adhesive 12 to inhibitcontact of adhesive 12. Package 20, which includes top layer 22 andbottom layer 24, contains implant 10 including adhesive 12 and releasesheet 15. It is envisioned that top layer 22 of package 20 may be openedor peeled away from bottom layer 24 to access implant 10 while adhesive12 remains covered by release sheet 15. Implant 10 may then bepositioned at the site of implantation by medical personnel whilerelease sheet 15 remains in contact with adhesive 12. Medical personnelmay then remove release sheet 15 from implant 10 to expose adhesive 12and position the adhesive 12 directly into contact with the targettissue for a period of time sufficient for adhesive 12 to form a bondwith the target tissue.

In other embodiments, as shown in FIG. 2, top layer 22 of package 20includes an internal surface 25, a portion of which is release sheet 15.As described herein top layer 22 of package 20 may be opened or peeledaway from bottom layer 24 to access implant 10 including adhesive 12.Top layer 22 includes a portion of which acts as a release sheet. Thetop layer may itself be made from a material that acts as a releasesheet, or as shown in FIG. 2 top layer 22 may have release sheet 15adhered thereto. Upon removal of bottom layer 24, top layer 22 willremain with implant 10 to protect against inadvertent contact withadhesive 12. Once implant 10 has been properly positioned, medicalpersonnel may then remove top layer 22 (including release sheet 15) fromimplant 10 to expose adhesive 12 and position adhesive 12 directly intocontact with the target tissue for a period of time sufficient foradhesive 12 to form a bond with the target tissue.

The package may be any conventional enclosure for storing implants. Someexamples of useful packages include, but are not limited too, pouches,paper retainers, plastic retainers, bags, trays, envelopes, Tyvek® bags,foil-packs, and the like. It is envisioned that the packages may besealable, non-sealable, breathable, non-breathable, peelable,resealable, and combinations thereof.

The package may be manufactured from any material known to those skilledin the art which is suitable for receiving or storing an implant. Someexamples of suitable materials include, but are not limited to,polycarbonate, high-density polyethylene, polyethylene, polypropylene,thermoplastic elastomers, thermosets, thermoplastic resins, metalizedpolymers, poly(ethylene terephthalate), polytetrafluoroethylene,ε-caprolactone, glycolide, l-lactide, d,l-lactide, d-lactide,meso-lactide, trimethylene carbonate, 4,4-dimethyl-1,3-dioxan-2-one,p-dioxanone, dioxepanone, δ-valerolactone, β-butyrolactone,ε-decalactone, 2,5-diketomorpholine, pivalolactone,α,α-diethylpropiolactone, 6,8-dioxabicyclooctan-7-one, ethylenecarbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione,3,3-dimethyl-1,4-dioxane-2,5-dione, polyolefins, polysiloxanes,polyalkylene glycols, polyacrylates, aminoalkyl acrylates,polyvinylalcohols, polyvinylpyrrolidones, polyoxyethylenes,polyacrylamides, poly(2-hydroxy-ethylmethacrylate), polymethacrylamide,dextran, alginic acid, sodium alginate, polysaccharides, gelatin andcopolymers, homopolymers, and block copolymers thereof.

The package is dimensioned and configured to receive an implant. In someembodiments, the package may include a single cavity for receiving theimplant. In other embodiments, the package may include more than onecavity for receiving the implant and the adhesive separately. Forexample, as shown in FIGS. 3A and 3B, package 20 may include a firstcavity 26 containing an adhesive 12 and a second cavity 28 positionedadjacent first cavity 26 and configured to contain implant 10. Package20 further includes rupturable barrier 35 which is positioned betweenfirst cavity 26 and second cavity 28. Upon rupture of rupturable barrier35, adhesive 12 can communicate with at least a portion of second cavity28.

It is envisioned that prior to implantation, the barrier may be pierced,broken, removed or opened to allow the adhesive contained in the firstcavity to flow onto at least a portion of the implant contained in thesecond cavity thereby positioning the adhesive on at least a portion ofthe implant. In embodiments, the barrier may be formed by a portion ofthe top and bottom layers of packaging. In other embodiments, thebarrier may be a separate member positioned between the first and secondcavity, which when exposed to a certain force, e.g., pressure,temperature, etc., the barrier will break or move to allow for thepassage of the adhesive from the first cavity to the second cavity. Asfurther shown in FIG. 3B, top layer 22 and bottom layer 24 of package 20may be heat-sealed around the perimeter of package 20 and may be peeledapart to open package 20 to remove implant 10 having at least a portionof adhesive 10 positioned thereon.

Turning now to FIG. 4, a dispenser 50 is shown including compartment 60for containing package 20 of the type shown in FIG. 3A having a firstcavity 26 containing a medical adhesive 12, a second cavity 28configured to contain a medical implant 10 and a rupturable barrier 35therebetween. Compartment 60 further includes a dispensing opening 70and a structure 80 for rupturing the rupturable barrier 35. Becausecompartment 26 is thicker than opening 70, pulling package 20 out ofcompartment 60 through opening 70 will result in rupture of rupturablebarrier 35. Structure 80 in this embodiment is a contoured ridge thatreduces the size of opening 70 and provides a smooth surface againstwhich package 20 is compressed to rupture rupturable barrier 35 withouttearing open compartment 36. In this manner, adhesive 12 can move intocompartment 28 without leaving the interior of package 20. Thus,dispensing opening 70 is designed and configured to allow for thepassage of the packaged implant out of compartment 60, but only afterthe rupturable barrier has been ruptured and at least some of adhesive12 moves into cavity 28 and into contact with implant 10.

As package 20 is withdrawn from dispenser 50, structure 80 appliespressure, pierces or forces open rupturable barrier 35 thereby allowingadhesive 12 to flow from first cavity 26 to second cavity 28. Dispenser50 may further include structure 90 for distributing the adhesive overat least a portion of implant 10. Examples of structures capable ofdistributing the adhesive to at least a portion of the implant include,but are not limited to, rollers, brushes, wipers and the like. Inparticularly useful embodiments, the dispenser will include at least oneroller to assist in spreading the adhesive onto the implant as thepackage is withdrawn from the dispenser.

It is envisioned that following the removal of the packaged implant fromthe dispenser, the package may be opened to expose the coated implant.In some embodiments, the coated implant may remain in a portion of thepackage, typically the bottom portion of the package, so that the coatedimplant may be manipulated without prematurely attaching to anunintended surface.

In some embodiments, as shown in FIGS. 6A-6C, dispenser 450 includesdispensing opening 470 and compartment 460 for containing implant 410,rupturable barrier 435 and adhesive 412. Dispenser 450 is shownpivotably connected to surgical introducer 500 which is used to positionimplant 410 at the site of implantation. It is envisioned thatintroducer 500 may be used to guide dispenser 450 through any surgicalopening or trocar to the site of implantation.

As shown in FIG. 6B, dispenser 450 may pivot or articulate to one sideof introducer 500 thereby breaking open rupturable barrier 435 andreleasing adhesive 412 on implant 410. As dispenser 450 is articulatedin the opposite direction as shown in FIG. 6C, implant 410 may exit orbe withdrawn from dispenser 450 via dispensing opening 470 andpositioned at the site of implantation. The adhesive will react with thetissue or fluids at the site of implantation securing the implant to thetissue. Once implant 410 is outside dispenser 450, dispenser 450 mayreturn to the straight position as shown FIG. 6A for removal from insidethe body.

It is envisioned that dispenser 450 may include additional structureswhich may be helpful in rupturing rupturable barrier 435 or useful inapplying adhesive 412 to implant 410. Some examples are described hereinand include, but are not meant to limited to, rollers, brushes, wipers,and the like.

In some embodiments implant 410 may be coated with an adhesive which isdesigned to react only with the tissue located at the site ofimplantation and as a result does not react with the implant, thedispenser thereby eliminating the need for a rupturable barrier 435. Insome embodiments, implant 410 may include adhesive 412 covered by arelease sheet which upon implantation may be removed or dissolved toexpose the adhesive on the implant.

The self-adherent implants described herein may additionally include abioactive agent. The bioactive agent may be combined with the materialused to form the implant and/or the adhesive. In addition, the bioactiveagent may be applied to a portion of the implant and/or adhesive. Theterm “bioactive agent”, as used herein, is used in its broadest senseand includes any substance or mixture of substances that have clinicaluse. Consequently, bioactive agents may or may not have pharmacologicalactivity per se, e.g., a dye, or fragrance. Alternatively a bioactiveagent could be any agent which provides a therapeutic or prophylacticeffect, a compound that affects or participates in tissue growth, cellgrowth, cell differentiation, an anti-adhesive compound, a compound thatmay be able to invoke a biological action such as an immune response, orcould play any other role in one or more biological processes. It isenvisioned that the bioactive agent may be applied to the implant in anysuitable form of matter, e.g., films, powders, liquids, gels and thelike.

Examples of classes of bioactive agents which may be utilized inaccordance with the present disclosure include anti-adhesives,antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics,antihistamines, anti-inflammatories, cardiovascular drugs, diagnosticagents, sympathomimetics, cholinomimetics, antimuscarinics,antispasmodics, hormones, growth factors, muscle relaxants, adrenergicneuron blockers, antineoplastics, immunogenic agents,immunosuppressants, gastrointestinal drugs, diuretics, steroids, lipids,lipopolysaccharides, polysaccharides, and enzymes. It is also intendedthat combinations of bioactive agents may be used.

Anti-adhesive agents can be used to prevent adhesions from formingbetween the implants and the surrounding tissues opposite the targettissue. In addition, anti-adhesive agents may be used to preventadhesions from forming between the implants and the packaging material.Some examples of these agents include, but are not limited to poly(vinylpyrrolidone), carboxymethyl cellulose, hyaluronic acid, polyethyleneoxide, poly vinyl alcohols and combinations thereof.

Suitable antimicrobial agents which may be included as a bioactive agentin the present disclosure include triclosan, also known as2,4,4′-trichloro-2′-hydroxydiphenyl ether, chlorhexidine and its salts,including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidinehydrochloride, and chlorhexidine sulfate, silver and its salts,including silver acetate, silver benzoate, silver carbonate, silvercitrate, silver iodate, silver iodide, silver lactate, silver laurate,silver nitrate, silver oxide, silver palmitate, silver protein, andsilver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such astobramycin and gentamicin, rifampicin, bacitracin, neomycin,chloramphenicol, miconazole, quinolones such as oxolinic acid,norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin,penicillins such as oxacillin and pipracil, nonoxynol 9, fusidic acid,cephalosporins, and combinations thereof. In addition, antimicrobialproteins and peptides such as bovine lactoferrin and lactoferricin B maybe included as a bioactive agent in the present disclosure.

Other bioactive agents which may be included as a bioactive agent inaccordance with the present disclosure include: local anesthetics;non-steroidal antifertility agents; parasympathomimetic agents;psychotherapeutic agents; tranquilizers; decongestants; sedativehypnotics; steroids; sulfonamides; sympathomimetic agents; vaccines;vitamins; antimalarials; anti-migraine agents; anti-parkinson agentssuch as L-dopa; anti-spasmodics; anticholinergic agents (e.g.oxybutynin); antitussives; bronchodilators; cardiovascular agents suchas coronary vasodilators and nitroglycerin; alkaloids; analgesics;narcotics such as codeine, dihydrocodeinone, meperidine, morphine andthe like; non-narcotics such as salicylates, aspirin, acetaminophen,d-propoxyphene and the like; opioid receptor antagonists, such asnaltrexone and naloxone; anti-cancer agents; anti-convulsants;anti-emetics; antihistamines; anti-inflammatory agents such as hormonalagents, hydrocortisone, prednisolone, prednisone, non-hormonal agents,allopurinol, indomethacin, phenylbutazone and the like; prostaglandinsand cytotoxic drugs; estrogens; antibacterials; antibiotics;anti-fungals; anti-virals; anticoagulants; anticonvulsants;antidepressants; antihistamines; and immunological agents.

Other examples of suitable bioactive agents include viruses and cells,peptides, polypeptides and proteins, analogs, muteins, and activefragments thereof, such as immunoglobulins, antibodies, cytokines (e.g.lymphokines, monokines, chemokines), blood clotting factors, hemopoieticfactors, interleukins (IL-2, IL-3, IL-4, IL-6), interferons (β-IFN,(α-IFN and γ-IFN), erythropoietin, nucleases, tumor necrosis factor,colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin,anti-tumor agents and tumor suppressors, blood proteins, gonadotropins(e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growthhormone), vaccines (e.g., tumoral, bacterial and viral antigens);somatostatin; antigens; blood coagulation factors; growth factors (e.g.,nerve growth factor, insulin-like growth factor); protein inhibitors,protein antagonists, and protein agonists; nucleic acids, such asantisense molecules, DNA and RNA; oligonucleotides; polynucleotides; andribozymes.

Now turning to FIG. 5, a particularly useful method of preparingself-adherent implants as described herein is shown. Implant 150 isshown being moved horizontally around a series of rollers 130A-D.Implant 150, e.g., a polypropylene surgical mesh, is moved through bath140 which contains an adhesive solution 160 to be applied to at least aportion of implant 150. Although specifically shown as being dipped inbath 140, adhesive solution 160 can be applied to medical implant 150 inany suitable manner for coating the implant. After exiting bath 140,implant 150 proceeds between a set of pinch rollers 180, 190 which mayremove excess adhesive solution 160 and continues through a pair ofcutting edges 212, 214. The cutting edges 212, 214 may be forcedtogether to separate implant 150 into predetermined lengths and widths.Once the implant 150 is cut into size, a top layer 224 and a bottomlayer 222 of packaging material may be used to “sandwich” the cutimplant 150. Medical implant 150, sandwiched between top layer 224 andbottom layer 222, proceeds to enter a sealing device 230 wherein toplayer 224 and bottom layer 222 are cut and sealed along the outerperimeter around implant 150. Although specifically shown as being cutby cutting edges 212, 214 prior to being packaged and sealed, implant150 may be cut, packaged and sealed in any order suitable to producing asterilized medical implant as described herein.

Since the self-adherent implant is intended and designed to be insertedinto the human body, the implant must be sterilized prior to use. Thesterilization of the implant, the package which contains the implant andthe dispenser which dispenses the packaged implant may be sterilized atanytime, including before and after packaging of the implant. Thesterilization process can be performed using various methods known toone skilled in the art, including, gamma radiation and gaseoussterilization with steam or ethylene oxide.

It will be understood that various modifications may be made to theembodiments disclosed herein. For example, it is contemplated that bothsides of the implant can be coated with adhesive and that both layers ofthe package may serve as or include a release sheet. As another example,the structure for rupturing the rupturable barrier may be spring loaded,rather than a simple pair of rollers. As yet another example, the dualcompartment package may include in one compartment an implant coatedwith an inactivated adhesive and an activation solution in the secondcompartment, rather than an uncoated implant and an adhesive asdescribed above. The activating solution may be water or a compositioncontaining initiators, crosslinkers, diluents and the like. Therefore,the above description should not be construed as limiting, but merely asexemplifications of preferred embodiments. Those skilled in art willenvision other modifications within the scope and spirit of the claimsappended hereto.

1-7. (canceled)
 8. A dispenser for activating packaged implants, saidpackaged implants having a first cavity containing a medical adhesive, asecond cavity configured to contain a surgical mesh and a rupturablebarrier therebetween, said packaged implants being activated by therupture of said rupturable barrier by said dispenser comprising: acompartment for containing said packaged implant, said compartmentincluding a dispensing opening and a structure for rupturing saidrupturable barrier.
 9. The dispenser of claim 8 wherein the medicaladhesive is selected from the group consisting of polyurethanes,isocyanates and combinations thereof.
 10. The dispenser of claim 8wherein the rupturable barrier is formed by a portion of a top layer anda bottom layer of the package.
 11. The dispenser of claim 8 wherein thestructure for rupturing said rupturable barrier comprises a contouredridge which reduces the size of the opening and includes a smoothsurface to rupture the rupturable barrier without tearing open thepackage.
 12. The dispenser of claim 8 further comprising a secondstructure for applying the medical adhesive to at least a portion of themesh.
 13. The dispenser of claim 12 wherein the second structure forapplying the medical adhesive is selected from the group consisting ofwipers, rollers, brushes and combinations thereof.
 14. The dispenser ofclaim 13 wherein the structure for applying the medical adhesive is aroller.
 15. The dispenser of claim 8 wherein the package is peelable.16. A dispenser for activating a packaged implant, said dispensercomprising: a compartment for containing a packaged implant, thecompartment including a dispensing opening and a structure for rupturinga rupturable barrier, the packaged implant including a medical adhesiveand a surgical mesh contained within a peelable package, wherein thepeelable package has a top layer and a bottom layer which together forma sealed perimeter of the peelable package, a first cavity defined bythe top and bottom layers and containing the medical adhesive, a secondcavity defined within the sealed perimeter of the peelable package andcontaining the surgical mesh, and a rupturable barrier positionedbetween the first and second cavity.
 17. The dispenser of claim 16wherein the medical adhesive is selected from the group consisting ofpolyurethanes, isocyanates and combinations thereof.
 18. The dispenserof claim 16 wherein the rupturable barrier is formed by a portion of atop layer and a bottom layer of the package.
 19. The dispenser of claim16 wherein the structure for rupturing said rupturable barrier comprisesa contoured ridge which reduces the size of the opening and includes asmooth surface to rupture the rupturable barrier without tearing openthe package.
 20. The dispenser of claim 16 further comprising a secondstructure for applying the medical adhesive to at least a portion of themesh.
 21. The dispenser of claim 20 wherein the second structure forapplying the medical adhesive is selected from the group consisting ofwipers, rollers, brushes and combinations thereof.
 22. The dispenser ofclaim 21 wherein the second structure for applying the medical adhesiveis a roller.